View Program - 63rd Annual Drosophila Research Conference

In different anterior-posterior (A-P) locations of the body, there are different circuits that control specialized functions. For example, humans have appendages (arms that are anterior, legs posterior to the trunk) that have unique movement patterns. Circuits at different A-P locations must process different sensory stimuli to generate specific movements. Spinal cord injury at different A-P levels gives different phenotypes. Injury in more anterior regions leads to paralysis of all 4 limbs whereas more posterior injuries result in paralysis of lower limbs, and regenerative treatments would need to generate region-specific circuits. The vertebrate spinal cord is segmented and develops from stem cells. In each segment, there are ~10 different progenitor domains that give rise to specific sets of spinal neurons. These 10 progenitor domains are repeated in every segment along the A-P axis. Stem cells have enormous therapeutic potential to regenerate circuits, but first we must understand how stem cells give rise to the A-P diversity of circuits during development. What are circuit variations in the spinal/ nerve cord along the A-P axis? And how are these circuit variations established in development? I am developing the Drosophila larval nerve cord as a model to address this question. Similar to the progenitor domains in the vertebrate spinal cord, the Drosophila nerve cord has a repeating set of ~30 stem cells called neuroblasts, which differentiate into neurons that wire up to form circuits. Here, I am characterizing the A-P circuit diversity of one neural stem cell lineage called neuroblast 3-3 (NB3-3). These NB3-3 stem cells are found in every segment of the Drosophila nerve cord and give rise to sensory processing even-skipped lateral (EL) interneurons. We are testing which properties of EL circuits are position-dependent vs position-independent. First, we assayed how ELs vary across the A-P axis of the Drosophila nerve cord in number, birth timing, and morphology using molecular and temporal identity markers, and stochastic labeling techniques. We are investigating diversity in sensory encoding of ELs by determining anatomical and functional input synaptic partnerships using transsynaptic circuit tracing and calcium imaging. This will tell us the diversity of somatosensory processing circuits in the nerve cord, as well as the diversity in how stem cells give rise to these circuits along the A-P axis. In the future, we can test genetic and cellular mechanisms that establish this A-P variation in circuit development.

Establishing anterior-posterior diversity in how stem cells give rise to neural circuits for somatosensory processing